SU502605A3 - Method for preparing imidazole derivatives - Google Patents

Description

a salt of a lower alkanoic acid, for example, is refluxed with an excess of ammonium acetate in glacial acetic acid. A corresponding oxazole is formed.

In another way, oxazoles are obtained by dehydrating the amide of the general formula

in, -co-to,

i

Bj-ch-tjfi

where Ri, RS and Hz are as defined above,, on: irimer by boiling with thionyl chloride in the Presence. or in the absence of an inert solvent, for example benzene, until hydrogen chloride ceases to form, or by treatment with co-concentrated sulfuric acid At 0 ° C to room temperature .

Example, a) Benzyl- (Z-pyridyl) -keton.

To a mixture of 27.4 g (0.2 lgol) of nicotinic acid methyl ester and 30 g (0.2 mol) of phenylacetic acid methyl ester is added in portions at 20-25 ° C under a nitrogen atmosphere of 16.2 g ( 0.3 mol of sodium methoxide. The reaction mixture is stirred at C for 20 hours, the resulting alcohol is blown off with a weak stream of nitrogen, and then 60 ml of concentrated hydrochloric acid is poured onto the solid mass and rinsed 3 hours in reverse with a cold refrigerant. 30 ml of water are poured into the hot yellow solution and cooled to 50 ° C. Then 60 ml of chloroform are added and the reaction the ionic mixture is cooled to 5 ° C. The white crystals formed are filtered on a suction filter and washed with chloroform. The temperature of crystal melting is 225 ° C (from ethanol).

b) 1-Phenyl-2- (3-, pyridyl) -glyoxal.

23.4 g (0.1 mol) of benzyl- (3-pyridyl) -: ketan-gi drochloride are dissolved in 180 ml of dimethyl sulfoxide and 20 ml of 48% hydrobromic acid are poured in. The reaction mixture is stirred for 18 hours at 80-85 ° C and then poured into a mixture of 800 g of ice and 1000. WATER.The yellow emulsion is extracted twice with 200 ml of ethyl acetate. Both organic phases are combined, washed with water and dried over sodium sulfate. The red solution is concentrated in a rotated (A boiling kettle prior to receiving as a residue 1 oil that is distilled in a tube with ball expansion m at 140-150 ° C / 0.1 mm Hg. v. Temperature pllzleni -Getting soedineni 56-57 ° C.

| h) 2-Oxy-2- (Z-yuridil) -shastofenon.

To a solution of 1.2.6 g (60 mmol) of 1-phenyl-2 (3-pyridyl) -glyoxal in 180 of absolute methanol Ex. Add in portions during peremeshiva: at 3-6 ° C for 30 minutes 970 mg (17.34 mmol) potassium bortirid. The reaction solution was stirred for 40 minutes at C, 50 g of ice, 100 ml 5 l were added. hydrochloric acid and methanol is distilled off in vacuo. To the remaining yellow aqueous solution is added 100 g of ice and 300 ml 2 and. sodium carbonate solution and extracted with ethyl acetate. The organic phase is washed with a saturated solution of sodium chloride, dried over atrium sulphate and evaporated, leaving 2-hydroxy-2- (3-pyridyl) -acetophenone as an oil.

d) 2-Pivaloyloxy-2- (3-: Pyridyl) - acetophenol.

To a mixture of 3.5 g (16.4 mmol) of 2-hydroxy-2- (3-pyrid. Yl) acetophe. Non, 2.7 ml of tri-ethylamine and 40 ml of absolute benzene was added dropwise at 22 ° C (initial temperature) solution 2.91 a

(27 mmol) of pivalic acid chloride in 15 ml of absolute benzene. The temperature is below 30 ° C. The suction is stirred for 4 hours at 40 ° C, 50 ml of water are poured and (Stir for 0.5 hour

at 20-25 ° C. Then 100 ml of ethyl acetate is added and the mixture is washed with 2N. sodium carbonate solution and saturated sodium chloride pacTiBopOM. The organic phase is separated, dried over sulfate.

rub and evaporate. The residue is dissolved in toluene and filtered through a column of saturated 100 g of silica-gel. The filtrate is discharged, and 2-1Pivaloyloxy-2- (3-pyridyl) acetophenone remains as lyric, mp. 73-76 ° C, primed to be further without purification.

d) 2-tert-butyl-4-phenyl-5- (3-pyridyl) -oxazole.

A mixture of 2.6 g (8.7 mmol) of 2-pavaloyloxy-2 (3-liridyl) acetophenone, 50 g of pivalic acid and 50 g of the ammonium salt of pivalic ACID is stirred at 110 ° C for 1 hour. The hot pacTiBop is poured into the mixture. 200 g of ice and 180 ml of a concentrated aqueous solution of ammonia and exgrated with methylene chloride. The organic phase is washed with concentrated W2N ammonia solution and saturated sodium chloride solution, dried over sodium sulfate and evaporated. The residue is chromatographed with a 20-fold amount of silica gel. Get 2-g / 7g-butyl4-phenyl-5- (3-lyridyl) -oxazole iB in the form of oil.

e) 2-t /) er. -butyl-4 (5) -phenyl-5 (4) - (3-pyr dil) -i, midazol.

A mixture of 2.78 g (10 mmol) of 2-tert-butylAphenyl- 5- (3-pyridyl) -oxazole with 30 g of liquid ammonia and 21 g of formamide is heated in a 5 -iac autoclave at 200 C. At this pressure

autoclave rises to 185 atm. After cooling, the mixture is poured into water and extracted with ethyl acetate. The organic phase is separated, washed with a saturated solution of sodium chloride and neutralized, dried over sodium sulfate, and evaporated. The residue was diluted with toluene-ethyl acetate (50:50) and filtered through a column, saturated with 50 g of silica gel. The filtrate is evaporated and the residue is recrystallized from toluene, and 2-tert-butyl-4 (5) -phenyl-5 (4) - (3-pyridyl) -imidazole is obtained, and the pl. 188-189 ° C

Similarly to paragraph 1e, from 2-g / eet.-butyl-4 (/ g-L1 methoxyphenyl) -5- (3-pyridyl) -oxazole with ammonia you get | 2-greg.-butyl-4 (5) - (g-methoxyphenyl ) -5 (4) - (3-pyridyl) - imidazole, so pl. 202-204 ° С (from toluene), and from 2 - ("- chlorophenyl) -4- (p-methoxyphenyl) -5- (3 - pyridyl) oxazole - 2 - (" - chlorophenyl-4 (5) - / g-methoxyfgnyl) -5 (4) - (3-1Pir: idyl) -imidazole, so pl. 200-203 ° C.

P p mi e p 2. To a solution of 27.8 g (0.10 mtol) 2-7 / 7e.-butyl-4 (5) - | phenyl - 5 (4) - (3-pyridyl) imidazole in 900 ml acetone tsribavla at 20-25 ° C 9.61 g (6.5 ml of 0.10 mmol of methanesulfonic acid, and then stirred for an hour. The white crystals are filtered on a suction filter. After recrystallization from ethanol-ether, the resulting 3-g / 7g -butyl-4 (5) -phenyl-5 (4) - (Znpyridyl) imidazole-methanesulfonate melts at 238-240 ° C.

Claims (2)

1. A process for the preparation of imidazole derivatives of the general formula N where RI is lower alkyl, cycloalkyl or phenyl, substituted with the corresponding case in halogen, lower alkyl or lower al “oxy group; one of the groups R2 and Rs is phenyl, substituted in the corresponding case; in the case of halogen, lower alkyl, hydroxy, lower alkyxyl group, lower alkylthio. or lower al.kylsulfonyl, and the second is wider, heteroaromatic residue with 1-2 / ring nitrogen atoms, and their N-oxides or salts, characterized in that they are subjected to the interaction of Viyu oxazole of the general formula Yli. EZ R, where RI, Ra. and Ra are as defined above, with ammonia, releasing the desired product in its free form, being converted to N-oxide or, in salt, by known methods. 2. The method of claim 1, wherein ammonia is used in the form of an amide. Priority (software: 11.05.71 when RI is alkyl, cycloalkyl containing at most 6 carbon atoms, or phenyl, unsubstituted or substituted by fluorine, chlorine or bromine, methyl, ethyl, methoxy-, or ethoxy; R2 is phenyl, unsubstituted or substituted by: chloro, methyl, methoxy-, ethoxy-, methyl-THYO--, ethylthiogrupoy, methylsulfonyl, ethylsulfonyl or oxy group; RS - lIridine, pyrazine. 03.03.72 when RI is lower alkyl, cycloalkyl, phenyl, substituted in the appropriate case by halogen, lower alkyl or lower alkoxy? POI; one of the groups Rg and RS is phenyl, substituted in the appropriate case by halogen, lower alkyl, hydroxy, lower alkyl, hydroxy, lower alkylthio group, or lower alkylsulfonyl, and the other is six-membered, heteroaromatic residue with 1-2 ring nitrogen atoms.